American Journal of Obstetrics and Gynecology
Meeting paperSMFM paperPreImplantation Factor (PIF) orchestrates systemic antiinflammatory response by immune cells: effect on peripheral blood mononuclear cells
Section snippets
PIF peptide isolation and synthesis
Partial characterization and PIF assay information was published previously.21, 22 Briefly, 1 L of mouse embryo that had been conditioned in culture media or control media was filtered through a 3 kd YM membrane (Millipore Corporation, Bedford, MA) and was passed through an affinity column (Anti-CD2 T11-1-antibody; BD Pharmingen, San Diego, CA) with Affi-Gel Hz Immunoaffinity (Bio-Rad Laboratories, Hercules, CA).32 Eluted fractions with PIF activity passed through C18 (Clipeus) high-performance
Predicted 3-dimensional structure; homology to malaria protein
Isolation of PIF from conditioned mouse embryo culture media vs media alone, control was carried out (Figure 1). PIF is a 15 aa peptide; where the first 9 aa are common for all 4 peptides (Figure 2, A and B). Figure 1, C and D, shows a predicted 3-dimension PIF (15 aa) image. We found that the 15 aa peptide (PIF) is by far the most abundant peptide in the embryo culture media, based on mass spectrometry. Therefore, the sPIF 15 aa (sPIF) was used for all experiments that assessed its interaction
Comment
Pregnancy-associated compounds inherently provide a fertile field of investigation for immune modulation without suppression, tolerance development, inflammation, and engraftment control. Herein, we document that PIF, an embryo-secreted peptide, modulates systemic human PBMC function. We demonstrate that sPIF offers a dual complementary mode of action that is highly dependent on the immune scenario that is involved: basal or challenged. In naïve PBMCs, sPIF binds macrophages and reduces TH1/TH2
Acknowledgments
We thank P.C. Leavis (Boston Biomedical Research Institute, Boston, MA), R.R. Gonzalez, (formerly of the Boston Biomedical Research Institute), and M. Barzani (Bio-Synthesis, Inc, Lewisville, TX) for their assistance in isolating and synthesizing PreImplantation Factor; C. Wiggins (Bioinformatics Solutions Inc, Waterloo, Ontario, Canada) for assistance in the 3-dimensional structure of PreImplantation Factor; A. Bulman (Ciphergen Systems, Freemont, CA) for analyzing the embryo culture media; R.
References (33)
- et al.
Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon?
Immunol Today
(1993) - et al.
Extinguishing maternal immune responses during pregnancy: implications for immunosuppression
Semin Immunol
(2001) - et al.
Placental MHC class I antigen expression is induced in mice following in vivo treatment with recombinant interferon-gamma
J Reprod Immunol
(1991) - et al.
Soluble monocyte cluster domain 163, a new global marker of anti-inflammatory response, is elevated in the first trimester of pregnancy
J Thromb Haemost
(2004) - et al.
NK cells and human pregnancy–an inflammatory view
Trends Immunol
(2006) - et al.
Th2 immune deviation induced by pregnancy: the two faces of autoimmune rheumatic diseases
Reprod Toxicol
(2006) Th1-type immunity is incompatible with successful pregnancy
Immunol Today
(1997)- et al.
Embryo-placento-maternal interaction and biomarkers: from diagnosis to therapy: a workshop report
Placenta
(2007) - et al.
Preimplantation Factor (PIF) negates embryo toxicity and promotes embryo development in culture
Reprod BioMedicine Online
(2011) - et al.
A genomic and proteomic investigation of the impact of preimplantation factor on human decidual cells
Am J Obstet Gynecol
(2010)
PreImplantation Factor promotes first trimester trophoblast invasion
Am J Obstet Gynecol
Kinetics of circulating preimplantation factor (PIF) levels during pregnancy
J Reprod Immunol
Human reproductive failure: I, immunological factors
Hum Reprod Update
Insight into early pregnancy events: the emerging role of the embryo
Am J Reprod Immunol
Prediction of Implantation in ART using molecular biology
Signaling between embryo and mother in early pregnancy: basis for development of tolerance
Cited by (42)
Novel therapeutic targets in autoimmune hepatitis
2018, Journal of AutoimmunityPreImplantation Factor (PIF*) endogenously prevents preeclampsia: Promotes trophoblast invasion and reduces oxidative stress
2016, Journal of Reproductive ImmunologyImmune regulatory and neuroprotective properties of preimplantation factor: From newborn to adult
2015, Pharmacology and TherapeuticsCitation Excerpt :In contrast, “scrambled PIF” (same amino acids as PIF, but in random order, used as control) had no effect, indicating that the PIF effect is selective. PIF regulates PBMCs cytokine secretion and related gene expression (Barnea, 2007b; Barnea, Kirk, et al., 2012; Barnea, Rambaldi, Paidas, & Mecacci, 2013). PIF reduced cytokines in unstimulated PBMCs.
Supported in part by a grant from the Consortium for Industrial Collaboration in Contraceptive Research of CONRAD (Arlington, VA), a Division of the Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA (E.R.B., principal investigator).
PreImplantation Factor (PIF) is a proprietary compound owned by BioIncept, LLC. E.R.B. is its (uncompensated) Chief Scientist; J. H. Barnea LLD, (uncompensated) President and CEO, is majority shareholder. Yale University received an unrestricted grant (M.J.P.). S.R. and R.R. received funding from BioIncept, LLC. D.K. and B.R. declare no conflict of interest.
Cite this article as: Barnea ER, Kirk D, Ramu S, et al. PreImplantation Factor (PIF) orchestrates systemic antiinflammatory response by immune cells: effect on peripheral blood mononuclear cells. Am J Obstet Gynecol 2012;207:313.e1-11.